Cloning and characterization of the human homologue of a dystrophin related phosphoprotein found at the Torpedo electric organ post-synaptic membrane.
Cloning and characterization of the human homologue of a dystrophin related phosphoprotein found at the Torpedo electric organ post-synaptic membrane.
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在鱼雷电器官突触后膜上发现的抗肌营养不良蛋白相关磷蛋白的人类同源物的克隆和表征。
DOI：
10.1093/hmg/5.4.489
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发表时间：
1996
影响因子：
3.5
通讯作者：
Kunkel,LM
中科院分区：
文献类型：
--
作者：
Sadoulet-Puccio,HM;Khurana,TS;Cohen,JB;Kunkel,LM
肌营养不良蛋白是杜氏肌营养不良症（DMD）中不存在的蛋白质产物。在哺乳动物骨骼肌中，发现肌营养不良蛋白与几种整合和外周膜蛋白结合，形成称为肌营养不良蛋白糖蛋白复合物（DGC）的复合物。在表达序列标签（EST）数据库搜索，以确定新的肌营养不良蛋白相关基因，我们分离EST 00891显示57%的同源性，富含半胱氨酸的结构域的肌营养不良蛋白和定位于18q12.1-12.2。该EST与Torpedocalfornicapost-synaptic 87 kDa磷蛋白也有很高的同源性（90%）。用该EST筛选成人脑和骨骼肌cDNA文库，克隆了多个cDNA，它们编码与肌营养不良蛋白C-末端结构域同源的几种剪接形式。分离的最大开放阅读框架显示与Torpedo 87 kDa蛋白的94%同源性（86%同一性）和与肌营养不良蛋白的富含半胱氨酸和羧基末端结构域的50%同源性。分离的其他cDNA编码该基因的较小剪接形式，我们将其命名为短肌营养不良蛋白。肌营养不良蛋白mRNA的组织分布显示了五种不同的转录本，它们在不同组织之间优先表达。此外，针对Torpedo 87 kDa蛋白或人小肌营养不良蛋白的抗体证明，至少有三种剪接形式在人脑组织提取物中被翻译为蛋白质。
Dystrophin is the protein product which is absent in Duchenne muscular dystrophy (DMD). In mammalian skeletal muscle, dystrophin is found in association with several integral and peripheral membrane proteins, forming a complex known as the dystrophin glycoprotein complex (DGC). In an expressed sequence tag (EST) database search to identify new dystrophin related genes, we isolated EST00891 which showed 57% homology to the cysteine-rich domain of dystrophin and localized to 18q12.1–12.2. This EST is also highly homologous (90%) to theTorpedo californicapost-synaptic 87 kDa phosphoprotein. Screening human adult brain and skeletal muscle cDNA libraries with this EST resulted in cloning multiple cDNAs which encode several splice forms all homologous to the C-terminal domain of dystrophin. The largest open reading frame isolated shows 94% homology (86% identity) to theTorpedo87 kDa protein and 50% homology to the cysteine-rich and carboxy-terminal domains of dystrophin. The other cDNAs isolated encode smaller splice forms of this gene which we have named dystrobrevin. The tissue distribution of dystrobrevin mRNA shows five distinct transcripts which are preferentially expressed between different tissues. In addition, antibodies against either theTorpedo87 kDa protein or human dystrobrevin demonstrate that at least three of the splice forms are translated as proteins in human brain tissue extracts.